DL -DODECAHYDRO-8{62 -(t-BUTOXY OR BENZYLOXY)- 8a{62 -LOWER ALKYL-2-OXO-PHENANTHRENE-ALKANOIC ACIDS

ABSTRACT

This disclosure describes compounds of the class of dl-2,3,4,4a Beta ,4b Alpha ,5,6,7,8,8a,9,10-dodecahydro-8a Beta -lower alkyl-8 Beta -(t-butoxy or benzyloxy)-2-oxo-1-substitutedphenanthrenes useful as intermediates in the synthesis of biologically active steroid moieties.

United States Patent n91 Los [4 1 Sept. 25, 1973dl-DODECAHYDRO-8B-(t-BUTOXY OR BENZYLOXY)- SaB-LOWERALKYL-Z-OXO-PHENANTHRENE- ALKANOIC ACIDS Inventor: Marinus Los, Trenton,NJ.

Assignce: American Cyanamld Company,

Stamford, Conn.

Filed: Jan. 6, 1969 Appl. 190.; 789,421

Related US. Application Data Division of Ser. No. 372,690, June 4, i964,Pat. No. 3,446,849.

US. Cl. 260/5 14.5 Int. Cl. C07c 61/32 Field of Search 260/514.5

[56] References Cited UNITED STATES PATENTS 2,836,616 5/1958 Farrar260/468 Primary Examinerborraine A. Weinberger Assistant Examiner-RobertGerst] Att0rneyEdward A. Conroy, Jr.

[5 7 1 ABSTRACT 2 Claims, No Drawings DL -DODECAIIYDRO-SB-(T-BUTOXY ORBENZYLOXY)- 8AB-LOWER ALKYL-Z-OXO-PHENANTIIRENE-ALKANOIC ACIDS CROSSREFERENCE TO RELATED APPLICATION This application is a division of mycopending application Ser. No. 372,690, filed June 4, 1964 now PatentNo. 3446849.

BRIEF SUMMARY OF THE INVENTION This invention relates to new organiccompounds and, more particularly, it relates to novel compounds usefulin the synthesis of a biologically active steroid moiety.

The compounds of the present invention may be illustrated by thefollowing formula:

.OR 2 I wherein R is selected from the group consisting of benzyl andtertiary butyl, R is lower alkyl and X is selected from the groupconsisting of i fY; lower alkylf Y; V

t. p. ii lIOiiCII 1-10 ccmcm and DETAILED DESCRIPTION OF THE INVENTION 2l,-8aB-dimethyl-4,4aB,4ba,5,6,7,8,8a,9,IO-decahydro- 2(3H)-phenanthrone; d l -8B-t-butoxy-8aB-ethyl-lmethyl-4,4aB,4ba,5,6,7,8,8a,9,l0-decahydro-2(3I-I)- phenanthrone;d1-8B-benzyloxy-l ,8a/3-dimethyl-4,4afi,4ba,5,6,7,8,8a,9,10-decahydro-2(3H)- phenanthrone;dl-8B-benzyloxy-8aB-ethyl-l-methyl-4,4afi,4ba,5,6,7,8,8a,9,l0-decahydro-2(3H)- phenanthrone and the like.

The present compounds are prepared by using starting materials such as,for example, 2-lower alkylcyclohexane-l ,3-dione (compound I) in theflowsheet hereinafter which is reacted with methylvinyl ketone inthe'presence of an alkali metal hydroxide in alcohol and adding to thismixture benzene and pyrrolidine to form a l,6-dioxo-A -9-loweralkyloctalin (II). This material (II) is separated from the mixture andthen treated with sodium borohydride (preferably purified) in alcohol,preferably ethanol, to form a l-hydroxy-6-oxo- A "-9-lower alkyloctalin(III) which is separated from the mixture. This product (III) is thenconverted to lacyloxy-6-oxo-A -9-lower alkyloctalin (IV) by reaction ofsaid material (compounds III) with an acyl halide or an acyl anhydride,preferably acetic anhydride, and pyridine. This material (compounds IV)is then separated from thereaction mixture. Reaction ofl-acyloxy-6-oxo-9-lower alkyl-A -octalin (IV) with a lower alkylorthoformate, preferably ethyl orthoformate, in the presence ofa strongacid catalyst will form newl en o l ethers. For example, when ethylorthoformate is used in the above reaction, l-acyloxy-6-ethoxy-9- loweralkyl- A -hexahydronaphthalene is formed in quantitative yield. Thecrude enol ether (V) l acyloxy- 6-lower alkoxy-9-lower alkyl A-hexahydronaphthalene may then be hydrogenated catalytically to the newcompound l-acyIoxy-6-lower alkoxy-9-lower alkyl-trans-A -octalin (VI),which without purification, is warmed with aqueous acetic acid to givel-acyloxy-6-oxo-9-lower alkyl-trans-decalin (VII). The subject'mattershown hereinafter in the flowsheet as compounds IV through VII isdescribed and claimed in my copending application Ser. No. 360,404,filed Apr.

I6, 1964, now U.S. Pat. No. 3,331,856.

The l-acyloxy-G-oxo-Q-lower alkyltrans-decalin compound (VII) whenrefluxed with ethylene glycol and p-toluene-sulphonic acid in a solvent,yields 1- acyloxy-6,6 ethylenedioxy-9-lower alkyl-trans-decalin (XII)which in turn is readily converted. to 6,6-ethylenedioxy-l-hydroxy-9-lower alkyl-trans-decalin (XIII) by refluxingwith an alcoholic solution of an alkali metal hydroxide, preferablyethanolic potassium hydroxide.

When a l-hydroxy-6,6-ethylenedioxy-9-Iower alkyltrans-decalin (compoundXIII) is heated with benzyl chloride and sodium hydride, an excellentyield of the l-benzyloxy (compound XIV) derivative is formed. As anexample, l-hydroxy-6,6-ethylenedioxy-9-methyltrans-decalin with benzylchloride and sodium hydride yieldsl-benzyloxy-6,6-ethylenedioxy-9-methyl-transdecalin.

Hydrolysis of the 6,6-ethylenedioxy ketal function (compounds XIV) isreadily accomplished by warming the ketal with aqueous acetic acid.Mineral acids in an organic solvent miscible with water can also beused. As a specific example, when l-benzyloxy-6,6-ethylenedioxy9-methyl-trans-decalin (compound XIV) is warmed with 30%aqueous acetic acid, the product obtained in excellent yield isl-benzyloxy-6- oxo-9-methyl-trans-decalin (compound XV).

When the compounds, represented by formula (XV), in an inert solvent,preferably chloroform, are treated with bromine in the same solvent, anexcellent yield of the corresponding bromo derivative (XVI) is formed.As a specific example, when 1-benzyloxy-6-oxo-9- methyl-trans-decalin istreated with bromine in chloroform, a good yield ofl-benzyloxy-7-bromo-6-oxo-9- methyl-trans-decalin is formed.

The bromo compounds (XVI) are dehydrobrominated in excellent yields byheating under reflux a solution of (XVI) in dry dimethylformamidecontaining anhydrous lithium halide, preferably lithium chloride, andanhydrous lithium carbonate in an inert atmosphere. Such reactionyields, for example, I-benzyloxy-6-oxo-9-lower alkyl-N-trans-octalin(XVII). For example, when 1-benzyloxy-7brom o-6-oxo-9-methyl-trans-decalin is dehydrobrominated in dimethylformamide inthe presence of lithium chloride and lithium carbonate, an excellentyield of lbenzyloxy-6-oxo-9-methyl-N-trans-octalin is formed.

By the different route, the l-acyloxy-6-oxo-9-lower alkyl-trans-decalins(VII) of the general formula:

OCOR' R2 wherein R is lower alkyl and R is selected from the groupconsisting of hydrogen, lower alkyl, phenyl and substituted phenylradicals (i.e. tolyl, halophenyl, and the like), is dissolved in aninert solvent, preferably chloroform, bromine, preferably dissolved inthe same solvent, is then admixed with this solution to yield thecorresponding bromo derivative, for example, l-loweralkanoyloxy-7-bromo-6-oxo-9-lower decalin (VIII).

Dehydrobromination of this product is carried out by heating a solutionof product (VIII) in dimethylformamide with a lithium halide, preferablylithium chloride, and preferably in the presence of lithium carbonate,thereby yielding the corresponding A derivative (IX). Hydrolysis of thislatter product (IX) is carried out with a weak base, preferablypotassium bicarbonate, a mixture of water and an inert organic solvent,preferably ethanol, miscible with water to yield the correspondingl-hydroxy derivative (X) of the flowsheet hereinafter.

The l-t-butoxy-6-oxo-9-lower alkyl-A -trans-octalin (XI) is formed byreaction of the above-identified 1- hydroxy derivative (X) withisobutylene in an inert solvent, preferably methylene chloride, in thepresence of a strong acid catalyst, preferably phosphoric acidborontrifluoride.

The compounds (VIII through XI) in the flowsheet hereinafter aredescribed and claimed in my copending application Ser. No. 372,688,filed June 4, 1964, now U.S. Pat. No. 3,321,511, and compounds (XIVthrough XVII) in my copending application Ser. No. 372,716, filed June4, I964, now US. Pat. No. 3,321,488.

The compound OR B; H H\/ alkyl-transwherein R and R, are as definedabove is compound (XVIII), generic to (XVII and XI) as shown in theflowsheet, can be transformed by condensation with an alkyl formate,preferably ethyl formate, in the presence of an alkali metal alkoxide,preferably sodium methoxide, in an inert solvent, preferably benzene, tothe product (XIX). As a specific example, l-t-butoxy-6-oxo-9- methyl-A-transoctalin with ethyl formate and sodium methoxide in benzene givesan excellent yield of trans- 1,2,4a,5,6,7,8,8a-octahydro-4a-methyl-5-t-butoxy-2- oxo-l-naphthaldehyderepresented generically by (XIX).

These compounds may be represented by the formula:

HC=O

wherein R is selected from the group consisting of benzyl and tertiarybutyl and R is lower alkyl.

When compound (XIX) is reacted with a,/3-unsaturated ketones, preferablyvinyl ketones, in the presence of an alkali metal alkoxide, preferablypotassium-tbutoxide, in an inert solvent, preferably t-butanol, under aninert atmosphere, there is formed a compound of the formula (XX) in goodyield which may be illustrated as follows:

OR R2 l KI l a] v O CHO wherein R is lower alkyl, R is selected from thegroup consisting of t-butyl and benzyl and R" is selected from the groupconsisting of hydrogen, lower alkyl, lower alkyl acetate and lower alkylpropionate. As specific examples, when the compound trans-I,2,4a,5,6,7,8,8aoctahydro-4a-methyl-5-t-butoxy-2-oxo-1- naphthaldehydeis treated with methylvinyl ketone in tbutanol containing potassiumt-butoxide, there is obtainedtrans-l,2,4a,5,6,7,8,8a-octahydro-4a-methyl-5-t-butoxy-2-oxo-l-(3-oxobutyl)-l-naphthaldehyde. When methyl5-oxo-6-heptenoate is employed, then the product is methyl transl-formyl-l 2,4a,5,6,7,8,8a-octahydro-4a-methyI-5-t-butoxy-8,2-dioxo-I-naphthaleneheptanoate. When the corresponding benzylether of(XIX) is used, then the products are the corresponding benzylderivatives. Similarly, when lower alkyl-4-oxo-5-hexenoate is used inthe reaction Ris lower alkyl acetate in compounds represented by genericformula (XX).

The conversion of compounds represented by (XX) is readily accomplishedby treating a solution of (XX) in a water-miscible organic solvent,preferably dioxane, with an aqueous solution of an alkali metalhydroxide, preferably sodium hydroxide, in an inert atmosphere. As aspecific example, methyl trans-l-formyl- I,2,4a,5,6,7,8,8a-octahydro-4a-methyl-5-benzyloxy-8,2-dioxo-l-naphthaleneheptanoate, represented generically by formula(XX), on treatment with sodium hydroxide in aqueous dioxane yields d1-2,3,4,4afl,4ba,5,6,7,8,8a-decahydro-8aB-methyl-BB- acid,

wherein R is lower alkyl, R is selected from the group consisting oft-butyl and benzyl and R is selected from the group consisting ofhydrogen, lower alkyl, acetic acid and propionic acid. Where theabovementioned hexenoate is used in the reaction, R' for compoundsrepresented by (XXI) is acetic acid.

The compounds (XXII) of the flowsheet may be illustrated by the formula:

R2 OR wherein R is lower alkyl, R is selected from the group consistingof t-butyl and benzyl and R is selected fromthe group consisting ofhydrogen, lower alkyl, acetic acid and propionic acid.

The reduction of compounds (XXI to XXII) is carried out with hydrogenand a hydrogenation catalyst, preferably palladium on strontiumcarbonate. Two solvent systems are employed in the reduction. When XXI(R"' is -CH CH COOI-I or -Cl-I COOH) is the substrate, water containingone equivalent of an alkali metal hydroxide, preferably sodiumhydroxide, is used. When XXI (R is H or lower alkyl) is the substrate,an inert solvent, preferably benzene, is used. As a specific example,dl-8B-benzyloxy- 2,3,4,4afi,4ba,5,6,7,8,8a-decahydro-8afi-methyl-Z-oxo-phenanthrene-l-propionic acid (XXI, R is CH R is CH C H R' is CHCI-I COOI-I) on reduction with hydrogen in water containing oneequivalent of sodium hydroxide in the presence of palladium on strontiumcarbonate give d1 -8/3-benzyloxy-2,3,4,4aB,4ba,5,6,7,8,8a,9,IO-dodecahydro-Bafimethyl-2oxo-phenanthrene-l-propionicacid (XXII, R is CH R is CH C H R is CI-I CH COOH). Where thecorresponding acetic acid analog of (XXI, R' is CH COOI-I) is reducedwith hydrogen in water, the corresponding acetic acid compound (XXII, R'is CH COOH) is found.

Although the examples above are specific for R as methyl, the processesare equally applicable when R is lower alkyl and the invention includesthe compounds in which R is a loweralkyl radical.

In the flowsheet R, R R" and R' are as herein before defined and R islower alkyl.

When the compounds (XXII wherein R' is -CI-I CI-I COOH, or -CH COOH, Ris lower alkyl and R is benzyl or t-butyl) are treated with aceticanhydride-sodium acetate, good yields of compounds (XXIII or XXIIIA) areproduced. As a specific example, the treatment ofd1-8B-benzyloxy-2,3,4,4a/3,4ba, 5,6,7,8,8a,-9,lO-dodecahydro-8aB-methyl-2-oxophenanthrene-l-propionic acid (inwhich R is CH with acetic anhydride and sodium acetate gives in goodyield dl-l7a,B-benzyloxy-5-hydroxy-3,5-seco-4-nor- '5(l0),9(11)-D-homoestradien-3-oic acid, 3,5-lactone (XXIII, in which R is CHTreatment of (XXII, where R' is -CI-l COOI-I), yields dl-l3 loweralkyll7a-benzyloxyl ,4-bisnor-3,5-seco-5-hydroxy-D- homo-gona-5( l0),9(ll )-dien-3-oic acid, 3,5-lactone.

Reduction of compounds (XXIII) with hydrogen and a hydrogenationcatalyst, preferably palladium on strontium carbonate in an inertsolvent, such as benzene, gives, in excellent yield (compounds XXIV). Asfor example, dl-l7a,B-benzyloxy-5-hydroxy-3,5-seco- 4-nor-5( l0),9(l 1)-D-homoestradien-3-oic acid, 3,5- lactone (XXIII, wherein R is CH onreduction gives d l -l7a,B-benzyloxy-5-hydroxy-3,5-seco-4-nor-5( l0)-D-homoestren-3-oic acid, 3,5-lactone (XXIV, wherein R is CH Finally,when compounds (XXIV) are treated with a methyl magnesium halide, suchas the bromide, and the crude product allowed to stand in a mixture ofacetic and hydrochloric acids, compounds (XXV) are formed in good yield.For example, dl-l7a,B-benzyloxy-5-hydroxy-3,5-seco-4-nor-5(10)-D-homoestren-3-oic acid, 3,5-lactone (XXIV,wherein R is CR gives on treatment with methyl magnesium bromidefollowed by acid a good yield of d1-l9-nor-D-homotestosterone,benzylether (compound XXV, wherein R is CH This compound (XXV) can betransformed into the known biologically active compound dl-l9-nor-D-homotestosterone by removing the benyzl blocking group. This can beremoved by reduction with lithium in liquid ammonia after protecting theketo group as the ethylene-dioxy ketal, and subsequent acid hydrolysisof the ketal.

When the starting material is dI-l7aB-benzyloxy-5- hydroxy-3,5-seco-4-nor-5(10)D-homogonene-3-oic acid, 3,5-lactone (compounds XXIV, whereinR is C 11 the final product will be dl-I3-ethyl-l9-nor-D-homo-4-gonene-17aB-ol (compounds XXV, wherein R is ethyl and R is H).

The following examples describe the use of starting materials, sch as2-lower alkylcyclohexane-l,3-diones I EXAMPLE 1 Preparation ofl,6-dioxo-A -9-ethyloctalin (II) A mixture of 70.0 g.Z-ethylcyclohexane-l,3-dione (l), 62 ml. of methylvinyl ketone, 0.25 g.potassium hydroxide and 250 ml. absolute methanol are heated withstirring under reflux for 4 hours. Methanol and excess methylvinylketone are then removed by distillation at atmospheric pressure; Benzeneis added to the residue and the distillation continued until thetemperature of the vapours is 80C. indicating complete removal ofmethanol and water. Benzene is added to bring the volume of the solutionup to the original volume. The solution is cooled in an ice bath and 3ml. pyrrolidine is added. The solution is heated under reflux under aDean- Stark water separator for 1 hour when no more water isazeo-tropically distilling. The solution is cooled in ice, diluted withether and washed with 100 ml. water containing 15 ml. ofa 10%hydrochloric acid solution, followed'by 100 ml. water. The aqueousphases are combined and washed with-50 ml. ether. The combined organicphases are washed with three 100 ml. portions 'clohexane-l,3-dione forthe 2-ethylcyclohexane-l,3-

dione in the above reaction. For example, the 1,6- dioxo-A"9-methyloctalin and l,6-dioxo-A -9- propyloctalin are readily preparedby this procedure.

EXAMPLE 2 Preparation of 1-hydroxy6-oxo-A -9-ethyloctalin (III),

To an ice-cold stirred solution of 9.6 of 1,6-dioxo- A "9-9-ethyloctalinin 90 ml. absolute ethanol is added 200 mg. purified sodium borohydride.After minutes, 200 mg. sodium borohydride is added and after a further15 minutes, 160 mg. sodium borohydride. The stirring and cooling arecontinued for 15 minutes and then the solution is acidified with glacialacetic acid. The ethanol is removed under. reduced pressure and theresidue partitioned between chloroform and water. The aqueous phase iswashed with chloroform and the combined organic phases washed withsodium bicarbonate solution, dried and evaporated. The residue isdistilled, the product, .l-hydroxy-6-oxo-A-9- ethyloctalin, boils at165C. at 0.8 mm. The oil crystallizes and the analytical sample, meltingpoint 88.0-89.5C. is obtained by recrystallization from acetone-hexane.

By employing the appropriate l,6-dioxo-A"'-9- lower alkyloctalin in theabove reaction, the corresponding l-hydroxy-6-oxo-A'-9-loweralkyloctalin is producedl For example, the corresponding -9-methyloctalin, -9-propyloctalin, -9-butyl or isopropyloctalins may beprepared by this procedure.

EXAMPLE 3 Preparation of l-acetoxy-6-oxo-A -9-ethyloctalin A mixture of3.98 g. of l-hydroxy-6-oxo-A -9- ethyloctalin, 10 ml. acetic anhydrideand 2 ml. pyridine are heated on a steam bath for 1.5 hours. Thesolution is then poured into 300 ml. ice water wih stirring. Afterstirring for 1 hour, the aqueous mixture is extracted with ether and theether washed with water, saturated sodium bicarbonate solution, driedand evaporated. The 1-acetoxy-6-oxo-A -9-ethyloctalin is obtained as acolorless oil, weighing 4.2 g. and is used without further purification.

The above reaction, when condensed with the appropriatel-hydroxy-6-oxo-A "-9-lower alkyloctalin in presence of pyridine and theappropriate acyl anhydride or aroyl halide yields the corresponding 1-acyloxy -6-oxo-A"-9-lower alkyloctalin or l-aroyloxy- 6-oxo-A -9-loweralkyloctalin, for example, 1- propionyloxy-6-oxo-A "-9-propyloctalin or1- benzyloxy-6 oxo-A -9-methyloctalin respectively.

EXAMPLE 4 Preparation of l-acetoxy-6-ethoxy-9-methyl-A"hex'ahydro-naphthalene (V) To a solution of 44.4 grams (0.2 mole) ofI-acetoxy- 6-oxo-9-methyl-A -octalin in 44 ml. ethyl orthoformate, 4 ml.absolute ethanol and 200 ml. benzene is added 4 ml. of absolute ethanolsaturated with hydrogen chloride and the mixture is heated underrefluxing conditions for 2 hours. The mixture is cooled, diluted with anequal volume of ether and poured into 300 ml. of 5% sodium hydroxidesolution. After shaking thoroughly, the aqueous phase is discarded. Theorganic phase is washed with water, saturated brine, dried and thesolvent evaporated. The residue, a yellow mobile oil, which can becrystallized to a colorless hydroscopic solid is essentically pure1-acetoxy-6-ethoxy-9-methyl- A -hexahydronaphthalene as determinedspectroscopically. This material is used directly for the preparation ofl-acetoxy-6-ethoxy-9-methyl-trans-A -octalin (VI).

EXAMPLE 5 Preparation of l-acetoxy-6-ethoxy-9-ethyl-A'hexahydro-naphthalene (V) The crude l-acetoxy-6-oxo-A -9-ethyloctalin(4.2 g.) (Example 3), 5.6 ml. ethyl orthoformate, 1 ml. absoluteethanol, 1 ml. absolute ethanol saturated with hydrogen chloride and ml.benzene are heated under reflux for 2 hours. The solution is cooled,diluted with ether, and washed with 100 ml. of 5% sodium hydroxidefollowed by washings with water and saturated brine. The organic phaseis dried and evaporated to yield l-acetoxy-6-ethoxy-9-ethyl-A-hexahydronaphthalene as a pale yellow oil weighing 4.7 g. This is usedwithout further purification for the preparation of l-acetoxy-6-ethoxy-A-9-ethyl-trans-octalin.

In the above Examples 4 and 5, ethyl orthoformate is used, otherorthoformates may also be used such as methyl, propyl, butyl and thelike. Also other strong acid catalysts can be used in place of hydrogenchloride such as sulfuric acid.

When l-benzoyloxy, l-toluoyloxy or 1- halobenzoyloxy, -6-oxo-9-loweralkyl-A -octalin, prepared as for example, by reacting l-hydroxy-6-oxo-9-lower alkyl-A -octalin with benzoyl chloride or the like in pyridine,is substituted for l-acetoxy-6-oxo-9- lower alkyl-A -octalin, theproduct from the reaction is the corresponding l-benzoyloxy,l-toluoyloxy or I- halobenzoyloxy, --6-ethoxy-9-lower alkyl-Ahexahydro-naphthalene. When this starting material is employed, theproducts V through IX, illustrated on the flowsheet, have the I-acetoxygroup replaced by the l-benzoyloxy, I-toluoyloxy or I-halobenzoyloxygroup.

EXAMPLE 6' Preparation of l-acetoxy-6-ethoxy-9-methyl-trans-A octalin(VI) The crude enol ether of Example 4 (from 6.7 gramsl-acetoxy-6-oxo-9-methyl-A -octalin) is dissolved in 150 ml. absoluteethanol and hydrogenated at room temperature and atmospheric presure inthe presence of 400 mg. of 2% palladium-on-strontium carbonate. One moleof hydrogen is absorbed in 2 hours. The catalyst is removed byfiltration and the ethanol evaporated under reduced pressure. The cruderesidue of lacetoxy-6-ethoxy-9-methyl-trans-A-octalin is used directlyfor the preparation of l-acetoxy-9-methyl-6-oxotrans-decalin of Example8.

In the above reaction, other hydrogenation catalysts may be used such asfor example palladium on carbon,

etc.

EXAMPLE 7 Preparation of I-acetoxy-6-ethoxy-A-9-ethyl-transoctalin (VI)The crude enol ether of Example 5 (4.7 g.) from I- acetoxy-6-oxo-A"-9-ethyloctalin is dissolved in 200 ml. absolute ethanol and L g. of 2%palladium hydroxide on strontium carbonate is added. The catalyst andcompound are reduced with hydrogen at atmospheric pressure. One molarequivalent of hydrogen is absorbed. The catalyst is then removed byfiltration and the solvent evaporated under reduced pressure. Theresidue consisting predominantly of I-acetoxy-6-ethoxy-A-9-ethyI-trans-octalin weighs 4.7 g. and is used without furtherpurification.

Further, employing the procedure set forth in Examples 6 and 7 above andsubstituting an enol ether of the general formula:

where R and R are lower alkyl, for the l-acetoxy-6- ethoxy-9-methyl-A"-hexahydronaphthalene of Example 6 or the I-acetoxy-6-ethoxy-9-ethyl-A-hexahydronaphthalene of Example 7, and R is a radical selected from thegroup consisting of hydrogen, lower alkyl, phenyl and substituted phenylradicals, there is produced a compound of the general formula:

OCOR

wherein R and R are lower alkyl and R is a radical as described above.

EXAMPLE 8 Preparation of l-acetoxy-9-methy|-6-oxo-trans-decalin (VII)The crude l-acetoxy-6-ethoxy-9-methyl-trans-A octalin is warmed on thesteam bath for 0.5 hour with 60 ml. 50% aqueous acetic acid. Aftercooling, the solution is diluted with water and extracted with ether.The ether is washed twice with water followed by saturated sodiumbicarbonate solution. The organic phase is dried and the solventevaporated. The residue is crystallized from a small volume of hexane togive 4.1 grams (61%) of 1-acetoxy-9-methyl-6-oxo-transdecalin, meltingpoint 4649C.

EXAMPLE 9 Preparation of I-acetoxy-6-oxo-9-ethyl-trans-decalin (VII) Thecrude l-acetoxy-6-ethoxy-A -9-ethyl-transoctalin (4.7 g.) prepared as inExample 7 is heated on a steam bath with 20 ml. water and 20 ml. glacialacetic acid for 0.5 hour. The solution is cooled, diluted with water andextracted with ether. The ether is washed with water, saturated sodiumbicarbonate solution, dried and evaporated. The residue ofl-acetoxy-o-oxo- 9-ethyl-trans-decalin weighs 4.1 g. and is used withoutfurther purification.

Using the procedure described in Examples 8 or 9 above and reacting acompound of the formula:

where R and R are lower alkyl and R is a radical selected from the groupconsisting of hydrogen, lower alkyl, phenyl and substituted phenylradicals, with aqueous acetic acid will yield a compound of the formula:

OCOIt where R and R are as described above.

EXAMPLE 10 Preparation of l-acetoxy-7-bromo-6-oxo-9-methyltrans-decalin(VIII) A mixture of 1-acetoxy-6,6-ethylenedioxy-9-methyltrans-decalin(25 g.) and ml. 50% acetic acid are heated on the steam bath for 0.5hour. After cooling, the solution is diluted with water and extractedwith ether. The ether is washed with water, saturated sodiumbicarbonate, dried and evaporated. The residue ofl-acetoxy-6-oxo-9-methyl-trans-decalin weighs 20.5 g. The keto acetateis dissolved in ml. chloroform and cooled to 0C. To the stirred solutionis added dropwise a solution of 15.0 g. of bromine in 75 ml. chloroform.After the addition, the chloroform is removed under reduced pressure andthe residue crystallizes from ether to give 20.85 g. (74% overall) ofthe bromo ketone. The analytical sample obtained by recrystallizationsof the crude product from acetonehexane has a melting point l47-l48C. I

The compound l-acetoxy-7-bromo-6-oxo-9-ethyltrans-decalin is readilyprepared in good yield by the above procedure employing l-acetoxy-6,6-ethylenedioxy-9 -ethyl-trans-decalin in place of thelacetoxy-6,o-ethylenedioxy-9-methyl-trans-decalin.

EXAMPLE 11 Preparation of l-acetoxy-6-oxo-9-methyl-N-transoctalin (IX) Amixture of 27.6 g. of l-acetoxy-7-bromo-6-oxo-9- methyl-trans-decalin,25 g. of dry lithium chloride and 25 g. dry lithium carbonate in 400 ml.dry dimethylformamide are heated at reflux under nitrogen for 2 hours.The solution is cooled, diluted with water and extr'actedwith ether. Theether is washed twice with water, saturated brine, dried and evaporated.The residue crystallizes completely and weighed 18.0 g. (89%). Thismaterial is sufficiently pure for the next-reaction. An analyticalsample obtained by recrystallization from ether-hexane has a'meltingpoint 62.5-63.5C.

This process is also advantageously employed to producel-acetoxy-6-oxo-9-ethyl-A-trans-octalin in high yield by simplysubstituting l-acetoxy-7-bromo-6-oxo- 9-ethyl-trans-decalin forl-acetoxy-7-bromo-6-oxo-9- methyl-trans-decalin in the reaction.

EXAMPLE 12 Preparation of 1-hydroxy-6-oxo-9-methyl-A-transoctalin (X) Amixture of 17.4 g. of l -acetoxy-6-oxo-9-methyl-N- trans-octalin in 100ml. ethanol and 50 g. potassium bicarbonate in 150 ml. water are heatedunder reflux for 5.5 hours. The mixture is cooled, diluted with .waterand extracted with ether. The ether is.washed with water and saturatedbrine, dried and evaporated. The residue is crystallized fromether-hexane to give 10.2 g. of l-hydroxy-6-oxo-9-methyl-A-trans-octalin, melting point 8688C. The analytical sample has meltingpoint 8889C.

Substituting l-acetoxy-6-oxo-9-ethyl-A -trans-octalin for1-acetoxy-6-oxo-9-methyl-N-trans-octalin gives the corresponding 9-ethylderivative (X) in good yield.

EXAMPLE 13 Preparation of l-t-butoxy-6-oxo-9-methyl-N-transoctalin (XI)7 To 25 ml. of liquid isobutylene containing 0.5 ml. of 100% phosphoricacid saturated with boron trifluoride is added 5.0 g. ofl-hydroxy-6-oxo-9-methyl-A-transoctalin in 25 ml. dry methylenechloride. The mixture is shaken overnight at room temperature. Aftercooling the mixture in an ice-methanol bath, excess isobutylene isremoved by a stream of dry nitrogen and the residue is dissolved inmethylene chloride. The solution is washed thoroughly with saturatedsodium bicarbonate solution, dried and evaporated. The residue isdissolved in hexane and passed through a plug of neutral alumina.Evaporation of the solvent yielded 5.7 g. (87%) of crystalline t-butylether melting point 7273C.

The compound l-t-butoxy-6-oxo-9-ethyl-A -transoctalin is prepared inaccordance with the above procedure employing as the starting materiall-hydroxy-6- oxo-9-ethyl-A-trans-octalin in the place of l-hydroxy-6-oxo-9 -methyl-N-trans-octalin.

EXAMPLE 14 Preparation ofl-acetoxy6,6-ethylenedioxy-9-methyltrans-decalin (XII) The crudel-acetoxy-9-methyl-6-oxo-trans-decalin derived from 16 grams crudel-acetoxy-6-eth0xy-9 methyl-A" -hexahydronaphthalene by the series ofreactions described in Examples 4, 6 and 8 without purification of anyintermediates is heated in 250 ml. henzene containing 16 grams ethyleneglycol and 200 mg. p-toluenesulphonic acid under a Dean-Stark waterscparator for 4 hours. The cold benzene solution is diluted with 200 ml.ether and then washed successively with saturated sodium bicarbonatesolution, water and saturated brine. After drying the organic phase, thesolvents are removed under reduced pressure. The residue is diluted withan equal volume of hexane and kept at 0C. overnight. The crystallinemass is removed by filtration and washed with 20 ml. cold hexane. Totalyield of l-acetoxy-6,6-ethylenedioxy-9-methyl-trans-decalin is 9.7 grams(57% based on enol ether of Example 4), melting point l161l7C. isobtained.

In the above reaction ethylene glycol is used to protect the keto group,however, other alcohols can be used such as propandiol.

EXAMPLE 15 Preparation of1-acetoxy-6,6-ethylenedioxy-9-ethyltrans-decalin (XII) A. solution ofcrude l-acetoxy-6-oxo-9-ethyl-transdecalin (2.05 g.) prepared as inExample 9 dissolved in ml. benzene containing 2.05 g. ethylene glycoland 100 mg. p-toluenesulphonic acid is heated under reflux under aDean-Stark water separator until no more water is azeotropically removed(4.5 hours). The solution is cooled, diluted with ether and washed withsaturated sodium bicarbonate solution. The organic phase is then washedwith water followed by saturated brine, dried and the solvents removedunder reduced pres sure. The residue is crystallized from hexane to give1- acetoxy-6,6-ethylenedioxy-9-ethyl-trans-decalin. The analyticalsample obtained by recrystallizations of the product from acetone-hexanehas a melting point 78.5-79.5C.

A compound of the formula:

2 J 1 loo/w as exemplified by Examples 14 and 15 above, where R is loweralkyl and R is hydrogen, lower alkyl, phenyl or substituted phenylradical are prepared by reacting a compound of the formula:

where R and R are as described above, with benzene, ethylene glycol andan acid such as p-toluenesulphonic acid.

EXAMPLE 16 Preparation of1-hydroxy-6,6-ethylenedioxy-9-methyltrans-decalin (XIII) A mixture of10.72 grams 0.04 mole)I-acetoxy-6,6-ethylenedioxy-(-methyl-trans-decalin, 100 ml. ethanol and50 ml. 2N potassium hydroxide solution are heated under refluxingconditions for 2 hours. Most of the ethanol is removed by distillationunder reduced pressure, the residue is diluted with water and extractedwith ether. The ether is washed with water, saturated brine, dried andevaporated. The residue crystallizes completely to give 7.9 grams (84%yield) of 1-hydroxy-6,6-ethyIenedioxy-9-methyl-transdecalin, meltingpoint 7172C.

Employing the procedure of this example and substituting a l-acyloxyorl-aroyloxy-, -6,6-ethy1enedioxy- 9-lower alkyl-trans-decalin for1-acetoxy-6,6- ethylenedioxy-9-methyl-trans-decalin will yield thecorresponding 1-hydroxy-6,6-ethyIenedioxy-9-lower alkyl-trans-decalin.The l-hydroxy-6,6-ethylenedioxy- 9-ethyl-trans-decalin prepared by thismethod is a crystalline solid, melting point 9596C.

EXAMPLE 17 Preparation of1-benzyloxy-6,6-ethylenedioxy-9-methyl-trans-decalin (XIV, R =CI-I;,)

A mixture of 63 ml. benzyl chloride, 10.85 g. 1-hydroxy-6,6-ethylenedioxy-9-methyl-trans-decalin (XIII, R is CH and11.05 g. of a 54% suspension of sodium hydride in mineral oil is stirredand gradually heated. At 120125C. a vigorous exothermic reaction takesplace. When the reaction has subsided, a temperature of 130C. ismaintained for 1 hour. The mixture is diluted with benzene and filtered.The benzene and excess benzyl chloride are removed under reducedpressure and the residue distilled. The product, 1-benzyloxy-6,6-ethylene-dioxy-9-methyl-trans-decalin is distilled atl76-l82C. at 0.5 mm., (13.0 g.). The product (XIV, R is CH crystallizescompletely and the analytical sample (from hexane) has a melting point83-83.5C.

When l-hydroxy-6,6-ethylenedioxy-9-ethyI-transdecalin (XIII, R is C 11,)is used in the reaction with benzyl chloride, the product is1-benzoyIoxy-6,6- ethylenedioxy-9-ethyl-trans-decalin (XIV, R is C Hwhich distills at 182184C. at 0.05 mm.

EXAMPLE 18 Preparation of l-benzyloxy-6-oxo-9-methyl-transdecalin (XV, R=CH:,)

To a solution of 130 g. of1-benzyloxy-6,6-ethylenedioxy-9-methyl-trans-decalin (XIV, R is CH;,) in500. ml. glacial acetic acid is added 300 ml. water and the mixtureheated on the steam bath for 0.5 hour. Approximately 200 ml. glacialacetic acid are added and the heating continued for 1.5 hours. Aftercooling the mixture, it is diluted with water and extracted with ether.The ether is washed with water, saturated sodium bicarbonate solution,dried and evaporated. The residue is distilled and the product hasboiling point 157C. at 0.03 mm. The product can be crystallized fromhexane at 10C. to a solid melting point 4647C.

When l-benzyloxy-6,6-ethylenedioxy-9-ethyl-transdecalin (XIV, R, is C11,) is hydrolyzed in the same way as described above, the product isI-benzyloxy-6-oxo- 9-ethyI-trans-decalin (XV, R is C 11 EXAMPLE 19Preparation of l-benzyloxy-7-bromo-6-oxo-9-methyltrans-decalin (XVI, R=CI-I A stirred solution of 38.35 g. of l-benzyloxy-6-oxo-9methyl-trans-decalin in 500 ml. chloroform was cooled to 0C. and then25.9 g. of bromine in 175 ml. chloroform is added dropwise at such arate that there is never more than a small amount of free brominepresent. After the addition, the solution is poured into a saturatedaqueous sodium bicarbonate solution. The two phases are well shaken, thechloroform layer separates, is dried and evaporated. The residue (51.0g.) consisting mainly of l-benzyloxy-7-bromo-6-oxo-9-methyltrans-decalin(XVI, R is CH,,) is used without further purification. The compound canbe crystallized from acetone-hexane and the analytical sample melted at1l21 13C.

When 1-benzyloxy-6-oxo-9-ethyl-trans-decalin, (XV, R =C H is brominatedin the same way, the product is1-benzyloxy-7-bromo-6-oxo-9-ethyl-trans-decalin (XVI, R is C H which hasmelting point 139-140C.

EXAMPLE 20 140 Preparation of 1-benzyloxy-6-oxo-9-methyl-A"-transoctalin(XVII R =CH The crude 1-benzyloxy-7-bromo-6-oxo-9-methyltrans-decalin(51.0 g.) prepared as in Example 19 is dissolvedin 600 ml. drydimethylformamide and 35 g. of dry lithium carbonate and 35 g. of drylithium carbonate added. The mixture is stirred and heated at refluxunder nitrogen for two hours. The mixture is cooled and most of thesolids removed by filtration. The filtrate is diluted with water andextracted with ether, then ether washed with water, saturated brine,dried and evaporated. The residue is distilled to giveI-benzyloxy-6-oxo-9-methyl-A"-trans-0ctalin (XVII, R is CH as a paleyellow oil, boiling point 170C. at 0.5

When 1-benzyloxy-6-oxo-7-bromo-9-ethyl-transdecalin (XVI, R is C 11 isdehydrobrominated as described above, the product is1-benzyloxy-6-oxo-9-ethyl-A' trans-octalin (XVII, R is C l-I whichdistills at -l70C. at 0.1 mm.

EXAMPLE 21 Preparation oftrans-1,2,4a,5,6,7,8,8a-octahydro-4amethyI5-t-butoxy-2-oxo-1-naphthaldehyde(XIX, R,=CH R'=t-butyl) To a stirred suspension of dry sodium methoxide(from 0.74-g. sodium) in dry benzene under nitrogen i added 4.5 ml. ofredistilled ethyl formate in a gentle stream. After stirring at roomtemperature for 0.5 hour, the mixture is cooled to 0C. and 2.36 g. of1-t-butoxy-6-oxo-9-methyl-A -trans-octalin in 20 ml. dry benzene isadded dropwise. The solution is then stirred overnight at roomtemperature. Water and ether are added to the mixture. The water isseparated and the organic phase extracted twice with 1N potassiumhydroxide. The combined aqueous phases are acidified with 2.5M sodiumdihydrogen phosphate solution and thoroughly extracted with ether. Theether is washed with water, saturated brine, dried and evaporated. Theresidue (2.55 g.) consisting oftrans-1,2,4a,5,6,7,8,8aoctahydro-4a-methyI-5-t-butoxy-2-oxo-1-naphthaldehyde (XIX, R is CH R is C(Cl-I is used without furtherpurification.

EXAMPLE 22 Preparation of trans-1,2,4a5,6,7,8,8a-octahydro-4a- The aboveis prepared from 2.86 g.. of crude l-benzyloxy-6-oxo-9-methyl-A -octalin(XV, R is CH R is CH C l-l ethylformate (4.5 ml.), and sodium methoxide(from 0.74 g. sodium) in a manner similar to that described for thet-butoxy analog in Example 21. Thetrans-l,2,4a,5,6,7,8,8a-octahydro-4amethyl--benzyloxy-2-oxo-1-naphthaldehyde(XIX, R is CH R is CH C I-I (3.1 g.) is obtained as a pale yellow oiland used directly.

When the reactions described in Examples 21 and 22 use as startingmaterials the ethyl analog (R is C H the products are the correspondingethyl compounds.

EXAMPLE 23 Preparation oftrans-l,2,4a,5,6,7,8,8a-octahydro-4amethyl-S-t-butoxy-Z-oxo-I-(3-oxobutyl)-lnaphthaldehyde (XX, R =CH R' =C(CI-I R"=H) The crudel-t-butoxy-5*formyl-6-oxo-9-methyl-A trans-octalin (2.55 g.) isdissolved in 100 ml. dry benzene and the solvent removed to removetraces of water. This procedure is repeated. The residue is dissolved inml. dry t-butanol and 0.87 g.-freshly distilled methylvinyl ketoneadded. The air is displaced by nitrogen, the solution cooled down in anice bath and 1 ml. of a 1M solution of potassium t-butoxide in t-butanolis added. The solutionis left at room temperature overnight. Ether andwater are added and the aqueous phase thoroughly extracted with ether.Theether is washed with water, saturated brine, dried and-evaporated.The residue, a viscous pale yellow oil, of transl,2,4a,5 ,6,7,8,8a-octahydro-4a-methyl-5-t-butoxy-2-oxo-l-(3-oxobutyl)-l-naphthaldehyde (XX, R is CH R is C(CI-I R" is H) isused without further purification.

EXAMPLE 24 Preparation oftrans-l,2,4a,5,6,7,8,8a-octahydro-4amethyl-5-benzyloxy-2-oxo-l-(3-oxobutyl)-lnaphthaldehyde(XX, R,=Cl-I;,, R'=CH C H R"=H) Fromtrans-l,2,4a,5,6,7,8,8a-octahydro-4a-methyl-S-benzyloxy-Z-oxo-l-naphthaldehyde (XIX, R is CH R is CH -C H 3.1 g.crude as described in Example 22, 0.87 g. freshly distilled methylvinylketone and 1 ml. of a 1M solution of potassium t-butoxide in tbutanolthere is obtained by following the procedure as described in Example 23,trans-I,2,4a,5,6,7,8,-8aoctahydro-4a-methyl-5-benzyloxy-2-oxo-1-(3-oxobutyl)-l-naphthaldehyde, is obtained as a viscous pale yellow oilwhich is used without further purification.

When the procedures described in Examples 23 and 24 are carried throughwith the ethyl analog, the products obtained are the 4a-.ethylnaphthaldehydes.

EXAMPLE 25 l0 dioxo-l-naphthaleneheptanoate The above compound isprepared from trans- 1,2,4a,5,6,7,8,8a-octahydro-4a-methyl-5-benzyloxy-2- oxo-l-naphthaldehyde (XIX,R is CH R is CH C H and ethylvinyl ketone by the procedure described inExample 24.

EXAMPLE 26 Preparation of methyl trans-l -formyll,2,4a,5,6,7,8,8a-octahydro-4a-methyl-5't-butoxy-8,2-

(XX, R=CH R'=C(CI-I ,R"%H CH COOCH The crudetrans-1,2,4a,5,6,7,8,8a-octahydro-4amethyl-S-t-butoxy-Z-oxo-l-naphthaldehydeprepared in Example 21 is dissolved in 5 ml. dry t-butanol and 1.87 g.methyl 5-oxo-6-heptenoate added. After cooling the solution under anitrogen atmosphere, 1 ml. of a 1 molar solution of potassium t-butoxidein t-butanol is. added and the mixture kept at room temperatureovernight. The solution is diluted with water and ether and the aqueousphase thoroughly extracted with ether. The ether is washed with water,and saturated brine, dried and evaporated. The residue of methyltrans-lformyl-l ,2,4a,5 ,6,7,8 ,8a-octahydro-4a-methyl-5-tbutoxy-8,2-dioxo-l-naphthaleneheptanoate (XX, R is CH R is C(CI-Igh,R" is CI-I CI-I COOCI-I is obtained as a viscous, pale yellow oil, andis used without further purification. The methyl acetate analog, i.e.,where R" is CH,COOCH can also be prepared by this procedure using methyl4-oxo-5-hexenoate instead of 5-oxo-6-heptenoate.

EXAMPLE 27 Preparation of methyl trans-1-formyll,2,4a,5,6,7,8,8a-octahydro-4a-methyl-5-benzyloxy-8,2-dioxo-l-naphthaleneheptanoate (XX, R =CH R'=CH C I-I R"=CI-I CHCOOCH This is prepared from the crude trans- 1,2,4a,5,6,7,8,8a-octahydro-4a-methyl-S-benzyloxy-Z- oxo-I-naphthaldehyde, 3.1g., described in Example 22, l.87.g. of methyl 5-oxo-6-heptenoate and 1ml. of a 1M solution of potassium t-butoxide in t-butanol by theprocedure described in Example 26.

The product, methyl tran sl -formyl- 1,2,4a,5,6,7,8,8a-octahydro-4a-methyl-5-benzyloxy- 8,2-dioxo-l-naphthaleneheptanoate (XX, R is CH R is CH C H R" is cH cmcoocm isobtained as a pale yellow viscous oil and was used in this form withoutfurther purification. The methyl acetate analog of the above compound,i.e., where R" is CH COOCH can be prepared by this procedure with methyl4-oxo- S-hexenoate in place of methyl 5-oxo-6-heptenoate.

EXAMPLE 28 Preparation of d1-8B-t-butoxy-8aB-methyl-4,4afi,4ba,5,6,7,8,8a-octahydro-2(3H)-phenanthrone (XXI, R =CH R'=C(CI-IR"'=II) The crudetrans-l,2,4a,5,6,7,8,8a-octahydro-4amethyl-S-t-butoxy-Z-oxo-l-(3-oxobutyl)-1-naphthaldehyde prepared in Example 23 is dissolved in 25 ml. dioxane andcooled to 0C. A solution of 1.7 g. potassium hydroxide in 25 ml. wateris added and the air displaced by nitrogen. After standing at room tem-.

perature for 3 hours, ether and water are added to the mixture and theaqueous phase thoroughly extracted with ether. The ether is washed withwater and saturated brine, dried and evaporated. The residue iscrystallized from ether-hexane. The analytical sample crystallized fromhexane has the melting point 134-l 35C.

EXAMPLE 29 Preparation of dl-8B-benzyloxy-8aB-methyl-4,4aB,4ba,5,6,7,8,8a-octahydro-2(3H)-phenanthrone (XXI, R =CH R'=CH C HR"'=H) The above is prepared fromtrans-l,2,4a,5,6,7,8,8aoctahydro-4a-methyl-5 benzyloxy-2-oxo-l-(3-oxobutyl)-l-naphthaldehyde (prepared as in Example 24) in 25 ml. dioxaneand 1.7 g. potassium hydroxide in 25 ml. water as described in Example28. The crude product is chromatographed on alumina to yield dl-8/3-benzyloxy-8aB-methyl-4,4afi,4ba,5,6,7,8,8aoctahydro-2(3I-I)-phenanthrone.An analytical sample, recrystallized from methanol, has melting point109l C.

EXAMPLE 30 Preparation of d l -8B-benzyloxy-8afi, l -dimethyl-4,4aB,4ba,5,6,7,8,8a-octahydro-2(3I-I)-phenanthrone (XXI, R =CH R=CH C HR'=-.-CH

This is prepared fromtrans-l,2,4a,5,6,7,8,8aoctahydro-4a-methyl-5-benzyloxy-2-oxo-l-(3-oxopentyl)-1-naphthaldehyde (XX, R is CH R is CH C H by the proceduredescribed in Example 28 to give the productd1-8B-benzyloxy-8afl,l-dimethyl-4,4aB,4ba,5,6,7,8,8a-octahydro-2(3I-I)-phenanthrone (XXI, wherein R isCH R is CH C H and R is CH EXAMPLE 3] Preparation ofd1-2,3,4,4a/8,4ba,5,6,7,8,8adecahydro-8aB-methyl-8B-t-butoxy-Z-oxophenanthrene-l-propionicacid (XXI, R'=C(CH R"=CH CH COOI-I) Crude methyltrans-l-formyl-1,2,4a,5,6,7,8,8aoctahydro-4a-methyl-5-t-butoxy-8,2-dioxo-Inaphthaleneheptanoate (3.0 g.) prepared in Example 26 is dissolved inml. dioxane and 30 ml. of a l.6M solution of sodium hydroxide added. Themixture is stirred overnight at room temperature under nitrogen. Thesolution is diluted with water and extracted with ether. The aqueousphase is acidified with 6N sulphuric acid and rapidly extracted withether. The ether is washed twice with water followed by saturated brinesolution. The ether is dried and evaporated. The residue (2.0 g.) isexhaustively extracted with boiling cyclohexane. The cyclohexane isevaporated and the residue crystallized from acetonitrile. Theanalytical sample recrystallized from the same solvent has melting point88-89C. The acetic acid analog of this compound, where R' is -CI-I COOH,may be prepared employing the methyl acetate analog of compound (XX) inthe reaction.

EXAMPLE 32 Preparation ofdI-2,3,4,4afi,4ba,5,6,7,8,8adecahydro-SaB-methyl-SB-benzyloxy-Z-oxophenanthrene-l-propionicacid (XXI, R'=CH C H R"=CI-I,CH COOH) This is prepared from the crudemethyl trans-1- formyl-l ,2,4a,5,6,7,8,8a-octahydro-4a-methyl-5-benzyloxy-6,2-dioxo-l-naphthaleneheptanoate described in Example 27 in15 ml. dioxane and 30 ml. of a 1.6M solution of sodium hydroxide asdescribed in Example 31. The product, d l2,3,4,4a[3,4ba,5,6,7,8,8a-decahydro-8aB-methyl-8B-benzyloxy-2-oxo-phenanthrene-l-propi0nic acid is obtained as acrystalline solid. Recrystallization from acetonitrile gives ananalytical sample melting point l58l59C.

EXAMPLE 33 Preparation of dl-8B-t-butoxy-8afi-methyl-4,4a[3,4ba,5,6,7,8,8a,-9,l0-decahydro-2(3H)- phenanthrone, (XXII whereinR is CH;,, R is C(CH R' is H) A suspension of 25 mg. of 2% palladiumhydroxide on strontium carbonate in 5 ml. dry benzene is reduced withhydrogen at atmospheric pressure. When the reduction is complete 54.4mg. of dl-8B-t-butoxy-8aB- methyl-4,4aB,4ba,5,6,7,8,8a-octahydro-2(3H)-phenanthrone is added and the reduction continued. After 7 minutes, 4.54ml. of hydrogen has been absorbed and there is no further absorption.The catalyst is removed by filtration and the solvent removed underreduced pressure. The residue crystallized and the solid isrecrystallized from hexane at l0C. to givedl-8B-tbutoxy-8aB-methyl-4,4afl,4ba, 5,6,7,8,8a, 9,10-decahydro-2(3H)-phenanthrone, melting point 9798C.

EXAMPLE 34 Preparation of dl-8B-benzyloxy-8aB-methyl-4,4afl,4ba,5,6,7,8,8a,-9,10-decahydro-2(3H)- phenanthrone (XXII, whereinR is CH;,, R is CI-I C H and R is H) Reduction of 43.7 mg. ofdl-8B-benzyloxy-8afimethyl-4,4a,B,4ba,5,6,7,8,8a-octahydro-2(3H)-phenanthrone in benzene with 25 mg. of 2% palladium hydroxide onstrontium carbonate as described in Example 33 givesdl-8B-benzyloxy-8aB-methyl-4,4aB,4ba,5,6,7,8,8a,9,l0-decahydro-2(3H)-phenanthrone, melting pointl0l-102C.

EXAMPLE 35 Preparation ofdl-8B-benzyloxy-2,3,4,4a/34ba, 5,6,7,8-,8a,9,lO-dodecahydro-8aBmethyl-2-oxophenanthrene-l-propionic acid (XXIwherein R is CH R is CI'I C H and R' is CH CH COOH) A suspension of 1.0g. of 2% palladium hydroxide on strontium carbonate is reduced in 30 ml.water with hydrogen at atmospheric pressure and room temperature. Asolution of 3.94 'g. of d1-8B-benzyloxy- 2,3,4,4aB,4ba,5,6,7,8,8a-decahydro-8aB-methyl-2- oxo-phenanthrene-l propionic acid in10 ml. of 1N sodium hydroxide is added. When 1 molar equivalent ofhydrogen has been absorbed, the catalyst is removed by filtration andthe aqueous phase acidified with dilute hydrochloric acid. The aqueousphase is thoroughly extracted with ether, the ether washed with water,saturated brine, dried and evaporated. The residue (4.0 g.) of crudedl-8B-benzyloxy-2,3,4,4a/3,4ba,5,6,7,8,8a,9,l0-dodecahydro-8afimethyl-2-oxo-phenanthrene-I-propionicacid is used without further purification.

The procedures detailed in Examples 25 through 35 for the methylcompounds R =CH in generic formulas are equally ueful when R is C I-Iand yield the corresponding product. This also applies where R" ismethyl acetate (XX) and following reactions yield XXI and XXII where R'is CI-I COOI-I.

EXAMPLE 36 Preparation of d1-l7aB-benzyloxy-5-hydroxy-3 ,5-seco-4-nor-5(10),-9(1l)-D-homoestradien-3-oic acid, 4,5- lactone (XXIIIwherein R is CH and R is CH C H A solution of 4 g. of dl-SB-benzyloxy-2,3,4,4aB,4ba,-5,6,7,8,8a,9,10-dodecahydro-8aflmethyl-2-oxo-phenanthrene-l-propionicacid in 40 ml. acetic anhydride and 50 mg. anhydrous sodium acetate isheated under reflux under nitrogen for 4 hours. The solvents areevaporated under reduced pressure and the residue dissolved in ether andwater. The aqueous phase is thoroughly extracted with ether, the etherphase combined and washed successively with 1M sodium carbonatesolution, water and saturated brine. The ether is separated, dried andevaporated. The residue is crystallized from ether to give dl-17aB-benzyloxy-S -hydroxy3,5-seco-4-nor-5( l),9( l l )-D- homoestradien-3-oicacid, 3,5-lactone, melting point l30-131C.

EXAMPLE 37 Preparation of d1-l7aB-benzyloxy-5-hydroxy-3,5-seco-4-nor-5(l0)-D-homoestren-3-oic acid, 3,5-lactone (XXIV, wherein R is CH,and R is CI-I C H A suspension of 0.5 g. of 2% palladium hydroxide onstrontium carbonate in 40 ml. dry benzene is reduced with hydrogen atroom temperature and atmospheric pressure. Then 1.76 g. ofdl-17aB-benzyloxy-5- hydroxy-3,5-seco-4-nor-5( l0),9( l I)-D-homoestradien-3-oic acid, 3,5-lactone in 40 ml. dry benzene is addedand the reduction continued. During 22 hours, 135 ml. of hydrogen hadbeen absorbd and the catalyst is then removed by filtration and thesolvent evaporated. The residue is dissolved in ether and percolatedthrough a plug of florisil. The florisil is washed with more ether andthe combined ether solutions evaporated and the residue crystallizedfrom an ether-hexane mixture to give dl-l7aB-benzyloxy-5-hydroxy-3,5-seco-4-nor-5( l0)- D-homoestren-3-oic acid, 3,5- lactone, melting pointl23-l24C.

EXAMPLE 38 Preparation of d1-l9-nor-D-homotestosterone, benzyl ether(XXV wherein R is CH and R is Cl-l C l-l A solution of 0.5 g.dl-l7aB-benzyloxy-5-hydroxybenzyl3,5-seco-4-nor-5(l0)-D-homoestren-3-oic acid, 3,5- lactone in ml. etherand30 ml. benzene is cooled to --50C. under nitrogen and 2 ml. of a 3Msolution of methyl magnesium bromide in ether is added with stirringover 20 minutes. After stirring a further 1 hour at -50C., 2Nhydrochloric acid is added and the mixture warmed to room temperature.The organic phase is diluted with benzene and the aqueous phasethoroughly extracted. The organic phase is washed with a 1M sodiumcarbonate solution, water, dried and evaporated to give 0.55 g. of acolorless oil. The oil is dissolved in 15 ml. glacial acetic acid and1.5 ml. concentrated hydrochloric acid is added. The solution is allowedto stand under nitrogen at room temperature for 48 hours. The solventsare removed under reduced pressure and the residue dissolved in benzene.The benzene is washed with saturated sodium bicarbonate, water,saturated brine, dried and evaporated to give a crystalline residue.This is recrystallized from ethanol to give 300 mg.l9-nor-D-homotesterone, benzyl ether, melting point 18S188C. A puresample is prepared by recrystallization from a chloroform-ethanolmixture. The analytical sample has melting point 194195C.

The procedures outlined in Examples 36, 37 and 38 are equally applicablewhen R in the generic formula is ethyl. In this instance the productsare the corresponding ethyl compounds.

I claim:

1. A compound of the formula:

Ih-O

wherein R is selected from the group consisting of tbutyl and benzyl,and R is lower alkyl.

2. The compound according to claim 1 wherein R is and R is methyl;dl-8B-benzyloxy-2,3,4,4aB,4ba,5,6,7,8,8a,9,lO-dodecahydro-Safimethyl-2-oxophenanthrene-l-propionicacid.

2. The compound according to claim 1 wherein R1 is benzyl and R2 ismethyl; d1-8 Beta -benzyloxy-2,3,4,4a Beta ,4b Alpha ,5,6,7,8,8a,9,10-dodecahydro-8a Beta -methyl-2-oxo-phenanthrene-1-propionic acid.